{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T13:20:15Z","timestamp":1791984015882,"version":"4.4.0"},"reference-count":66,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T00:00:00Z","timestamp":1693958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p><jats:bold>Introduction:<\/jats:bold> The left (LV) and right (RV) ventricles are linked biologically, hemodynamically, and mechanically, a phenomenon known as ventricular interdependence. While LV function has long been known to impact RV function, the reverse is increasingly being realized to have clinical importance. Investigating ventricular interdependence clinically is challenging given the invasive measurements required, including biventricular catheterization, and confounding factors such as comorbidities, volume status, and other aspects of subject variability.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Computational modeling allows investigation of mechanical and hemodynamic interactions in the absence of these confounding factors. Here, we use a threesegment biventricular heart model and simple circulatory system to investigate ventricular interdependence under conditions of systolic and diastolic dysfunction of the LV and RV in the presence of compensatory volume loading. We use the end-diastolic pressure-volume relationship, end-systolic pressure-volume relationship, Frank Starling curves, and cardiac power output as metrics.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> The results demonstrate that LV systolic and diastolic dysfunction lead to RV compensation as indicated by increases in RV power. Additionally, RV systolic and diastolic dysfunction lead to impaired LV filling, interpretable as LV stiffening especially with volume loading to maintain systemic pressure.<\/jats:p><jats:p><jats:bold>Discussion:<\/jats:bold> These results suggest that a subset of patients with intact LV systolic function and diagnosed to have impaired LV diastolic function, categorized as heart failure with preserved ejection fraction (HFpEF), may in fact have primary RV failure. Application of this computational approach to clinical data sets, especially for HFpEF, may lead to improved diagnosis and treatment strategies and consequently improved outcomes.<\/jats:p>","DOI":"10.3389\/fphys.2023.1231688","type":"journal-article","created":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T19:27:11Z","timestamp":1694028431000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Computational modeling of ventricular-ventricular interactions suggest a role in clinical conditions involving heart failure"],"prefix":"10.3389","volume":"14","author":[{"given":"Salla M.","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. Benjamin","family":"Randall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filip","family":"Jezek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A.","family":"Beard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi C.","family":"Chesler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,9,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1161\/CIRCULATIONAHA.104.481465","article-title":"Contractile behavior of the left ventricle in diastolic heart failure: with emphasis on regional systolic function","volume":"113","author":"Aurigemma","year":"2006","journal-title":"Circulation"},{"key":"B2","doi-asserted-by":"publisher","first-page":"3213","DOI":"10.1016\/j.bpj.2022.07.029","article-title":"Reduced cardiac muscle power with low ATP simulating heart failure","volume":"121","author":"Beard","year":"2022","journal-title":"Biophys. J."},{"key":"B3","volume-title":"A physical approach to hemodynamic aspects of the human cardiovascular system","author":"Beneken","year":"1979"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1798","DOI":"10.1136\/heartjnl-2020-317342","article-title":"Right ventricle in heart failure with preserved ejection fraction","volume":"106","author":"Berglund","year":"2020","journal-title":"Heart"},{"key":"B5","first-page":"5887","article-title":"A 3D-1D-0D computational model for the entire cardiovascular system","volume":"29","author":"Blanco","year":"2010","journal-title":"Mec\u00e1nica Comput."},{"key":"B6","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1161\/CIRCHEARTFAILURE.109.930701","article-title":"'Exercise hemodynamics enhance diagnosis of early heart failure with preserved ejection fraction","volume":"3","author":"Borlaug","year":"2010","journal-title":"Circ. Heart Fail"},{"key":"B7","volume-title":"Medical physiology","author":"Boron","year":"2016"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1664","DOI":"10.1002\/ejhf.873","article-title":"Right ventricular dysfunction in left-sided heart failure with preserved versus reduced ejection fraction","volume":"19","author":"Bosch","year":"2017","journal-title":"Eur. J. Heart Fail."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1161\/01.cir.44.6.1072","article-title":"Evaluation of pulmonary arterial end-diastolic pressure as an estimate of left ventricular end-diastolic pressure in patients with normal and abnormal left ventricular performance","volume":"44","author":"Bouchard","year":"1971","journal-title":"Circulation"},{"key":"B10","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1161\/01.cir.100.7.761","article-title":"Acute right ventricular dilatation in response to ischemia significantly impairs left ventricular systolic performance","volume":"100","author":"Brookes","year":"1999","journal-title":"Circulation"},{"key":"B11","doi-asserted-by":"publisher","first-page":"H501","DOI":"10.1152\/ajpheart.00138.2005","article-title":"Assessment of systolic and diastolic ventricular properties via pressure-volume analysis: a guide for clinical, translational, and basic researchers","volume":"289","author":"Burkhoff","year":"2005","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B12","first-page":"401","article-title":"Assessment of atrioventricular valve regurgitation using biomechanical cardiac modeling","author":"Chabiniok","year":"2017"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1314","DOI":"10.1183\/09031936.02.00068002","article-title":"Haemodynamic evaluation of pulmonary hypertension","volume":"20","author":"Chemla","year":"2002","journal-title":"Eur. Respir. J."},{"key":"B14","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1007\/s10334-005-0025-8","article-title":"Normal range of human left ventricular volumes and mass using steady state free precession MRI in the radial long axis orientation","volume":"19","author":"Clay","year":"2006","journal-title":"Magma"},{"key":"B15","doi-asserted-by":"publisher","first-page":"3709","DOI":"10.1038\/s41598-021-82567-9","article-title":"Understanding and recognition of the right ventricular function and dysfunction via a numerical study","volume":"11","author":"Comunale","year":"2021","journal-title":"Sci. Rep."},{"key":"B16","doi-asserted-by":"publisher","first-page":"4556","DOI":"10.1093\/eurheartj\/ehaa159","article-title":"The 'Digital Twin' to enable the vision of precision cardiology","volume":"41","author":"Corral-Acero","year":"2020","journal-title":"Eur. Heart J."},{"key":"B17","doi-asserted-by":"publisher","first-page":"H1514","DOI":"10.1152\/ajpheart.1991.261.5.H1514","article-title":"Significant left ventricular contribution to right ventricular systolic function","volume":"261","author":"Damiano","year":"1991","journal-title":"Am. J. Physiol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.yjmcc.2015.12.006","article-title":"Cardiac muscle mechanics: sarcomere length matters","volume":"91","author":"de Tombe","year":"2016","journal-title":"J. Mol. Cell. Cardiol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1038\/nrcardio.2017.65","article-title":"Epidemiology of heart failure with preserved ejection fraction","volume":"14","author":"Dunlay","year":"2017","journal-title":"Nat. Rev. Cardiol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1016\/j.jacc.2004.03.060","article-title":"Cardiac power is the strongest hemodynamic correlate of mortality in cardiogenic shock: a report from the SHOCK trial registry","volume":"44","author":"Fincke","year":"2004","journal-title":"J. Am. Coll. Cardiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e007308","DOI":"10.1161\/CIRCHEARTFAILURE.120.007308","article-title":"Extracardiac abnormalities of preload reserve: mechanisms underlying exercise limitation in heart failure with preserved ejection fraction, autonomic dysfunction, and liver disease","volume":"14","author":"Fudim","year":"2021","journal-title":"Circ. Heart Fail."},{"key":"B22","doi-asserted-by":"publisher","first-page":"H1528","DOI":"10.1152\/ajpheart.01031.2005","article-title":"Impaired left ventricular filling due to right-to-left ventricular interaction in patients with pulmonary arterial hypertension","volume":"290","author":"GanTji-Joong","year":"2006","journal-title":"Am. J. Physiology-Heart Circulatory Physiology"},{"key":"B23","doi-asserted-by":"publisher","first-page":"2003","DOI":"10.1007\/s10439-014-1071-z","article-title":"Cardiac tissue structure, properties, and performance: a materials science perspective","volume":"42","author":"Golob","year":"2014","journal-title":"Ann. Biomed. Eng."},{"key":"B24","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1002\/ejhf.691","article-title":"Right ventricular dysfunction in heart failure with reduced vs. preserved ejection fraction: non-identical twins?","volume":"19","author":"Gorter","year":"2017","journal-title":"Eur. J. Heart Fail."},{"key":"B25","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1161\/CIRCHEARTFAILURE.112.000098","article-title":"Impaired left ventricular mechanics in pulmonary arterial hypertension: identification of a cohort at high risk","volume":"6","author":"Hardegree","year":"2013","journal-title":"Circ. Heart Fail."},{"key":"B26","doi-asserted-by":"publisher","first-page":"17136","DOI":"10.1038\/s41598-021-96618-8","article-title":"Right versus left ventricular remodeling in heart failure due to chronic volume overload","volume":"11","author":"Havlenova","year":"2021","journal-title":"Sci. Rep."},{"key":"B27","doi-asserted-by":"publisher","first-page":"3130","DOI":"10.1002\/ehf2.13419","article-title":"Right-ventricular dysfunction in HFpEF is linked to altered cardiomyocyte Ca(2+) homeostasis and myofilament sensitivity","volume":"8","author":"Hegemann","year":"2021","journal-title":"Esc. Heart Fail"},{"key":"B28","first-page":"1913","article-title":"The relative systolic discharges of the right and left ventricles and their bearing on pulmonary congestion and depletion","volume":"5","author":"Henderson","year":"1914","journal-title":"Heart"},{"key":"B29","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/s0079-6107(98)00013-3","article-title":"Modelling the mechanical properties of cardiac muscle","volume":"69","author":"Hunter","year":"1998","journal-title":"Prog. Biophysics Mol. Biol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"H1092","DOI":"10.1152\/ajpheart.00417.2010","article-title":"Kinetics of cardiac muscle contraction and relaxation are linked and determined by properties of the cardiac sarcomere","volume":"299","author":"Janssen","year":"2010","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.yjmcc.2021.09.013","article-title":"Systems analysis of the mechanisms governing the cardiovascular response to changes in posture and in peripheral demand during exercise","volume":"163","author":"Jezek","year":"2022","journal-title":"J. Mol. Cell. Cardiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"4991","DOI":"10.1113\/JP281845","article-title":"Phenotyping heart failure using model-based analysis and physiology-informed machine learning","volume":"599","author":"Jones","year":"2021","journal-title":"J. Physiol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"H882-H892","DOI":"10.1152\/ajpheart.00172.2020","article-title":"Biomechanics of diastolic dysfunction: a one-dimensional computational modeling approach","volume":"319","author":"Kadry","year":"2020","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B34","doi-asserted-by":"crossref","DOI":"10.1137\/1.9781611970920","volume-title":"Iterative methods for optimization","author":"Kelley","year":"1999"},{"key":"B35","doi-asserted-by":"publisher","first-page":"H403","DOI":"10.1152\/ajpheart.01240.2005","article-title":"Single-beat estimation of end-diastolic pressure-volume relationship: a novel method with potential for noninvasive application","volume":"291","author":"Klotz","year":"2006","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1186\/s12968-015-0220-3","article-title":"Left ventricular diastolic dysfunction in pulmonary hypertension predicts functional capacity and clinical worsening: a tissue phase mapping study","volume":"17","author":"Knight","year":"2015","journal-title":"J. Cardiovasc. Magnetic Reson."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1964","DOI":"10.1016\/j.jbiomech.2005.06.016","article-title":"Numerical simulation of cardiovascular dynamics with healthy and diseased heart valves","volume":"39","author":"Korakianitis","year":"2006","journal-title":"J. Biomech."},{"key":"B38","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.jcp.2012.09.015","article-title":"Patient-Specific models of cardiac biomechanics","volume":"244","author":"Krishnamurthy","year":"2013","journal-title":"J. Comput. Phys."},{"key":"B39","doi-asserted-by":"crossref","DOI":"10.1016\/B978-0-12-809657-4.99652-2","article-title":"Right heart catheterization","volume-title":"Encyclopedia of cardiovascular research and medicine","author":"Lampert","year":"2018"},{"key":"B40","article-title":"Chapter 6 - heart failure for the pulmonary critical care physician","volume-title":"Manual for pulmonary and critical care medicine","author":"Landsberg","year":"2018"},{"key":"B41","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1007\/s10741-015-9506-7","article-title":"Heart failure preserved ejection fraction (HFpEF): an integrated and strategic review","volume":"20","author":"Lekavich","year":"2015","journal-title":"Heart Fail Rev."},{"key":"B42","doi-asserted-by":"publisher","first-page":"2234","DOI":"10.1007\/s10439-009-9774-2","article-title":"Three-wall segment (TriSeg) model describing mechanics and hemodynamics of ventricular interaction","volume":"37","author":"Lumens","year":"2009","journal-title":"Ann. Biomed. Eng."},{"key":"B43","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.mbs.2018.07.001","article-title":"Practical identifiability and uncertainty quantification of a pulsatile cardiovascular model","volume":"304","author":"Marquis","year":"2018","journal-title":"Math. Biosci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"716597","DOI":"10.3389\/fphys.2021.716597","article-title":"An implementation of patient-specific biventricular mechanics simulations with a deep learning and computational pipeline","volume":"12","author":"Miller","year":"2021","journal-title":"Front. Physiology"},{"key":"B45","doi-asserted-by":"publisher","first-page":"e002922","DOI":"10.1161\/CIRCHEARTFAILURE.115.002922","article-title":"Fluid volume overload and congestion in heart failure: time to reconsider pathophysiology and how volume is assessed","volume":"9","author":"Miller","year":"2016","journal-title":"Circ. Heart Fail."},{"key":"B46","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1001\/jama.2020.10262","article-title":"Heart failure with reduced ejection fraction: a review","volume":"324","author":"Murphy","year":"2020","journal-title":"JAMA"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1474","DOI":"10.1093\/cvr\/cvx160","article-title":"The overloaded right heart and ventricular interdependence","volume":"113","author":"Naeije","year":"2017","journal-title":"Cardiovasc. Res."},{"key":"B48","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.yjmcc.2018.11.015","article-title":"A short history of the development of mathematical models of cardiac mechanics","volume":"127","author":"Niederer","year":"2019","journal-title":"J. Mol. Cell. Cardiol."},{"key":"B49","doi-asserted-by":"crossref","DOI":"10.1016\/B978-0-323-35885-9.00005-9","article-title":"Cardiovascular system: structure, assessment, and diseases","volume-title":"Plastics in medical devices for cardiovascular applications","author":"Padsalgikar","year":"2017"},{"key":"B50","doi-asserted-by":"publisher","first-page":"H691-H700","DOI":"10.1152\/ajpheart.00596.2016","article-title":"Why septal motion is a marker of right ventricular failure in pulmonary arterial hypertension: mechanistic analysis using a computer model","volume":"312","author":"Palau-Caballero","year":"2017","journal-title":"Am. J. Physiology-Heart Circulatory Physiology"},{"key":"B51","doi-asserted-by":"publisher","first-page":"2162","DOI":"10.1016\/j.jbiomech.2015.11.030","article-title":"Data assimilation and modelling of patient-specific single-ventricle physiology with and without valve regurgitation","volume":"49","author":"Pant","year":"2016","journal-title":"J. Biomechanics"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1598","DOI":"10.1161\/CIRCRESAHA.119.313572","article-title":"Heart failure with preserved ejection fraction in perspective","volume":"124","author":"Pfeffer","year":"2019","journal-title":"Circulation Res."},{"key":"B53","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1161\/CIRCULATIONAHA.108.844340","article-title":"Ventricular geometry, strain, and rotational mechanics in pulmonary hypertension","volume":"121","author":"Puwanant","year":"2010","journal-title":"Circulation"},{"key":"B54","doi-asserted-by":"publisher","first-page":"H293","DOI":"10.1152\/ajpheart.1992.263.1.H293","article-title":"A method to reconstruct myocardial sarcomere lengths and orientations at transmural sites in beating canine hearts","volume":"263","author":"Rodriguez","year":"1992","journal-title":"Am. J. Physiol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"e004121","DOI":"10.1161\/CIRCHEARTFAILURE.117.004121","article-title":"Load-independent systolic and diastolic right ventricular function in heart failure with preserved ejection fraction as assessed by resting and handgrip exercise pressure-volume loops","volume":"11","author":"Rommel","year":"2018","journal-title":"Circ. Heart Fail."},{"key":"B56","doi-asserted-by":"publisher","first-page":"0708041","DOI":"10.1115\/1.4043552","article-title":"On the simulation of mitral valve function in health, disease, and treatment","volume":"141","author":"Sacks","year":"2019","journal-title":"J. Biomechanical Eng."},{"key":"B57","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1152\/jappl.1976.41.6.925","article-title":"Left ventricular effects on right ventricular developed pressure","volume":"41","author":"Santamore","year":"1976","journal-title":"J. Appl. Physiol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1625","DOI":"10.21037\/cdt-20-370","article-title":"Diagnosis and treatment of right ventricular dysfunction in congenital heart disease","volume":"10","author":"Santens","year":"2020","journal-title":"Cardiovasc Diagn Ther."},{"key":"B59","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1016\/j.hlc.2013.03.072","article-title":"Right ventricular function in left ventricular disease: pathophysiology and implications","volume":"22","author":"Schwarz","year":"2013","journal-title":"Heart, Lung Circulation"},{"key":"B60","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1161\/CIRCRESAHA.115.302922","article-title":"Heart failure with preserved ejection fraction: mechanisms, clinical features, and therapies","volume":"115","author":"Sharma","year":"2014","journal-title":"Circulation Res."},{"key":"B61","doi-asserted-by":"publisher","first-page":"H684-H692","DOI":"10.1152\/ajpheart.00573.2018","article-title":"Right coronary artery ligation in mice: a novel method to investigate right ventricular dysfunction and biventricular interaction","volume":"316","author":"Sicard","year":"2019","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1136\/hrt.68.7.16","article-title":"Left ventricular filling characteristics in pulmonary hypertension: a new mode of ventricular interaction","volume":"68","author":"Stojnic","year":"1992","journal-title":"Br. Heart J."},{"key":"B63","doi-asserted-by":"publisher","first-page":"1291","DOI":"10.1056\/NEJMoa003417","article-title":"Impact of high-ormal blood pressure on the risk of cardiovascular disease","volume":"345","author":"Vasan","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"B64","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1513\/AnnalsATS.201312-446FR","article-title":"Management of acute right ventricular failure in the intensive care unit","volume":"11","author":"Ventetuolo","year":"2014","journal-title":"Ann. Am. Thorac. Soc."},{"key":"B65","doi-asserted-by":"publisher","first-page":"1801900","DOI":"10.1183\/13993003.01900-2018","article-title":"'Pathophysiology of the right ventricle and of the pulmonary circulation in pulmonary hypertension: an update","volume":"53","author":"VonkKelly Marie Chin","year":"2019","journal-title":"Eur. Respir. J."},{"key":"B66","doi-asserted-by":"publisher","first-page":"404","DOI":"10.6515\/ACS.202107_37(4).20210123A","article-title":"Prognostic value of right ventricular cardiac power output at rest in patients with advanced heart failure","volume":"37","author":"Yildiz","year":"2021","journal-title":"Acta Cardiol. Sin."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2023.1231688\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T19:27:22Z","timestamp":1694028442000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2023.1231688\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,6]]},"references-count":66,"alternative-id":["10.3389\/fphys.2023.1231688"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2023.1231688","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,6]]},"article-number":"1231688"}}